This proposal is intended to examine the changing patterns in the expression of the B-cell clonotype repertoire and the factors which control its expression and responsiveness as they pertain to the ageing process. Two specific aspects of this question will be analyzed. Firstly, techniques available to characterize B cells and identify clonotypes at the individual precursor cell level will be used to assess age-associated changes in clonotype representation in the various B-cell compartments. In this assessment, particular emphasis will be placed on analysis of the clonotypes expressed in immature bone marrow B cells (cells which are both tolerizable and capable of only IgM expression) as an index of the maintenance of the capacity to generate new B cells. Secondly, the "immunoregulatory status" of animals of various ages will be examined with respect to a recently defined "antibody-specific" immunoregulatory phenomenon. It has been shown that, after immunization, mice of an inbred strain develop the capacity to specifically suppress the responses to the immunogen of syngeneic primary B cells but not of primary B cells allogeneic with respect to heavy chain allotype and thus presumably idiotype. Since this suppression is long-lived, it may be presumed that individuals may normally accumulate such "anti-idiotypic" regulatory processes during their lifetime. Experiments will be carried out to analyze this phenomenon during the process of natural ageing with the aim of determining: a) whether aged animals maintain the capacity of generate this regulatory phenomenon and, if so, b) if aged animals suppress responses of syngeneic but not allogeneic (at allotype) primary B cells, and c) whether the B cells of aged animals are selectively less susceptible to such regulation.